Cu(II)-Catalyzed N-Directed Distal C(sp³)–H Heteroarylation of Aliphatic N-Fluorosulfonamides

Abstract

A copper-catalyzed δ-regioselective C­(sp3)–H heteroarylation of N-fluorosulfonamides has been developed. A broad range of heteroarenes were well tolerated and reacted with various N-fluorosulfonamides to give the corresponding heteroarylated amides in good yields. Notably, all types (1°, 2°, and 3°) of δ-C­(sp3)–H bonds in the N-fluorosulfonamides could be regioselectively activated through the 1,5-HAT process. This protocol provides a practical strategy for the functionalization of heteroarenes and amides via forging a C­(sp3)–C­(sp2) bond.

Remote C(sp3)–H heteroarylation of N-fluorocarboxamides with quinoxalin-2(1H)-ones under visible-light-induced photocatalyst-free conditions

“…After systematically surveying the reaction parameters, we were pleased to obtain the desired product 3aa in 85% NMR yield by performing the reaction of 1a (0.1 mmol), 2a (0.2 mmol), and LiOH (0.2 mmol) in 1,4-dioxane (1 mL) under nitrogen and irradiation with 24 W purple LEDs at room temperature without adding any photocatalysts (Table 1, entry 1). Notably, in sharp contrast to the previous radical functionalizations with N -fluoroamides as radical precursors, 13,15 the present reaction was promoted by visible light in the absence of a metal catalyst or an external photosensitizer. We also performed the reaction in other solvents, such as DMSO and CH 3 CN, and 83% and 80% yields were obtained, respectively (Table 1, entry 2).…”

“…Based on the above experiments and previous reports, 5 a–c ,13 a plausible mechanism is depicted in Scheme 6. Upon visible-light irradiation, quinoxalin-2(1 H )-ones absorb the light energy to become excited species 1a * or 3aa *, which next underwent a single electron transfer (SET) process with N -fluorobenzamide 2a to generate a radical cation 1a or 3aa , a fluoride anion and an amidyl radical I .…”

“…Over the past decade, only one example of site-specific C(sp 3 )–H heteroarylation of N -fluorosulfonamides with various quinoxalin-2(1 H )-ones was reported by Hao and Song (Scheme 1b). 13 However, this reaction requires a transition-metal catalyst, elevated temperature (100 °C), and a less attractive protecting group (Ts), which greatly limits its practical applications, especially in the pharmaceutical industry. Hence, the development of a general and “greener” methodology in the construction of functionally amidated quinoxalin-2(1 H )-ones via an amidyl-initiated 1,5-HAT process is highly desirable.…”

Copper-Catalyzed Hydrogen Atom Transfer and Aryl Migration Strategy for the Arylalkylation of Activated Alkenes

“…Recently, well-stabilized N -fluoroamides , / N -fluorosulfonamides , were widely used as an N-centered radical precursor due to the lower tendency of N–F bond homolytic cleavage compared to other N–X (X = Cl, Br) bonds, , which favors C­(sp 3 )–H bond functionalization after the 1,5-HAT process over C–X bond formation, as in the classic HLF reaction. In general, low-cost and low-toxicity copper catalysts are used to reduce N -fluoroamides/ N -fluorosulfonamides to amide/sulfonamide radicals, followed by a kinetically favored intramolecular 1,5-HAT process to afford key C-centered radicals, which couple with various nucleophilic organocopper complexes to achieve regioselective remote C­(sp 3 )–H arylation, trifluoromethylation, and amination (Scheme a). However, using an N–F substrate as the N-radical precursor to generate the key C-centered radical via the HAT process and then coupling with the alkene to regioselectively construct specific chemical structures remains a challenge.…”

Divergent regioselective Heck-type reaction of unactivated alkenes and N-fluoro-sulfonamides

“…In recent years, the alkyl radicals generated from N-fluoro-amides via a sequence involving single-electron transfer (SET) with transition metal or photocatalyst, followed by 1,5-hydrogen atom transfer (HAT) have been well studied in the construction of C-C and C-X bonds [44][45][46][47][48][49][50][51][52][53] . However, the interaction of N-fluoro-amides with alkenes has rarely been explored.…”